As if migraine weren't bad enough (it can be disabling) or widespread enough (it afflicts nearly one in five Americans), it also comes with a stigma that often renders it invisible.

That's a social stigma that somehow even extends to the medical research community, which largely has overlooked this neurological disease for years — to the public detriment.

So goes the plaint of Robert Shapiro, professor of neurology at the University of Vermont, practicing neurologist and headache specialist.

Shapiro just published a study, based partly on research on a Vermont family with a history of migraines, that identified a gene mutation associated with the condition. It was the eighth gene that's been pinpointed as connected to unusual forms of migraines. Most of the others were found by researchers in Europe, which Shapiro said is way ahead of the United States in this field.

Shapiro is a leading advocate for more funding of migraine and headache research in the U.S.

Migraine is a brain disorder that shows up as a syndrome. In the absence of biomarkers, or physical signs that can be measured, doctors have come up with diagnostic criteria, based on symptoms patients describe. Headache is the best known symptom and one of the most common, but it's possible to have migraine without one. Other common symptoms include nausea and sensitivity to light, sound and touch and aura symptoms.

Shapiro said migraine affects up to 60 million Americans with "enormous disability consequences" and an economic cost of $30 billion a year. Migraine headaches can last from four to 72 hours and vary in intensity.

According to Migraine Research Foundation, about 2 percent of the population suffer from "chronic migraine," that is, migraines that occur 15 days or more a month.

"What happens if you have this problem and can't afford to acknowledge it or you lose your job or you lose your family?" Shapiro said. "Lost work is measured as absenteeism. It's also measured by a condition called presenteeism, when people come to work because they're capable of passing. If you look at the lost work productivity as a consequence of headache disorders, 80 percent is presenteeism. These are people who heroically soldier on, but they're ineffective. They don't have any choice."

Shapiro, is one of only about 400 physicians certified as headache specialists by the United Council for Neurologic Subspecialties.

Individual experience

Migraines, Shapiro said, are "extremely individual, idiosyncratic. What one person experiences is often quite distinctly theirs," and the sufferer's same symptoms tend to recur from one attack to the next.

Infantile colic has been hypothesized to be a form of migraine, Shapiro said. Research tracking people who had colic as infants found a high prevalence of migraines among them in adolescence. The peak age for migraines to appear is late adolescence/early adulthood.

One of the risk factors is heredity — migraine runs in families. Other risks are believed to be environmental or substance exposures. Many medical conditions also increase risk, including hormonal changes (estrogen, for example), obesity, epilepsy, head trauma, sleep and affective disorders.

"Searching for genes is potentially a very productive angle to understanding what causes this brain state and therefore what might lead to potential therapies," Shapiro said.

Shapiro's recent research focused partly on a Vermont family with a history of both of migraine and a rare sleep disorder. Family members had a mutated gene that Shapiro and his colleagues were able to identify and that they suspected might be linked to both conditions. When that mutated gene was implanted in a line of mice, the mice litters exhibited features associated both with migraine and the sleep disorder.

Might this gene discovery lead to development of treatment or prevention?

"We're quite a ways from that. How far away it's hard to say," Shapiro said, "but the advantage here is, this is the first gene among the genes that have been found for migraine that isn't a code for a structural protein ... it's actually a regulator of other proteins."

Just one class of FDA-approved drugs, including sumatriptan, has been developed specifically to treat acute migraine, he said, but medications used for prevention were all developed for other purposes. One reason there aren't more targeted medications, he said, is that most drug development by pharmaceutical companies is sparked by findings of publicly funded research — research that is sorely lacking in the case of migraine.

Advocacy

Six years ago, Shapiro founded Alliance for Headache Disorders Advocacy, a consortium of 12 nonprofit organizations concerned with headache disorders. The aim is to push for policies that will lead to improved treatment — more funding for research from the National Institutes of Health, for example.

That has been a major thrust of an event the alliance has staged in Washington every year, known as Headache on the Hill, which brings doctors, other caregivers and headache sufferers from all around the country to lobby Congress.

"I know a lot of members of Congress have migraine," he said. "You cannot be very public about it." Why? Admitting you have a disabling condition can be "a career-killer." Rep. Michele Bachmann's campaign last year for the Republican presidential nomination, whatever its other challenges, was not enhanced by her acknowledgment that she suffered from migraine.

"I believe there will come a point, hopefully soon, when it will dawn on enough members of Congress where they will realize they can be a hero by pushing on an open door and saying, we have a problem that we can help fix."

Migraine isn't the only neglected condition, he said.

"Cluster headache is a good case in point," he said. "Cluster headache is widely regarded as the most severe pain a human can experience — that's not hyperbole. It has a population prevalence that's approximately the same as multiple sclerosis."

Over the past decade, Shapiro said, NIH has directed $1.872 billion to multiple sclerosis research, which he said is warranted. By contrast, less than $2 million has gone to cluster headaches over the last 25 years. "It's completely invisible," he said.

The advocacy campaign has yet to bear much fruit at NIH. True, funding for headache research rose 26 percent from 2010 to 2012, to $24 million, but that's still less than 0.1 percent of NIH's budget and below what it should be, in Shapiro's mind.

In a phone interview, Linda Porter, pain policy adviser at NIH, pointed to the increase in headache research funding but added that "we totally recognize that headaches need more funding." The challenges are, she said, that NIH budgets have been flat and the headache research community is a small one.